SCOR--LUNG BIOLOGY AND DISEASES IN INFANTS AND CHILDREN

这项建议旨在提高我们对各种因素的理解。 新生儿肺损伤的相关因素及其远期临床 后果。组成项目将检查急性肺病的基础。 损伤以及导致长期损伤的顺序 呼吸道结构和功能的改变。该中心将 除了确定的行政核心外，还包括6个主要项目 和该中心的方案需求。具体项目有：1)新生儿 肺基质驱动肺修复。这项研究将界定 氧化损伤对肺上皮细胞基底膜基质相互作用的影响 氧化损伤中的肺泡上皮细胞分化。这项研究将 检测氧化损伤对Na/K-ATPase和 肺中γ-谷氨酰基转移酶；3)应激蛋白之间的关系 以及高氧血症中的抗氧化剂。热冲击反应已经被证明是 在涉及损伤和修复的各种系统中发挥重要作用。我们 将检查热休克蛋白与内源性抗氧化剂的关系 高氧性损伤的机制：4)表面活性物质的调节 损伤成人和发育中肺的磷脂代谢。这 项目将研究表面活性磷脂在不同环境中的合成 二氧化硅致肺损伤后II型细胞的数量；5) 丁酸对SP-A基因转录的影响这个项目将 研究肺对一种特定的生化损伤的反应 基因表达的改变；6)婴儿呼吸的能量学 慢性肺病。在这个项目中，我们将研究肺部的变化。 BPD婴儿的工作、呼吸效率和能量消耗 代表了急性肺损伤的最终共同途径。该条例草案将会 包括2个核心，它将为方案提供支持， 教育和监督部分以及生物统计支持和 一个共享的仪器设备。一种共有的形态和电子显微镜 CORE将为组件实验室项目提供支持。这个 通过该中心提供的互动和共享知识将导致 更好地了解肺损伤的潜在事件 在合理的预防策略能够严格执行之前必不可少的 开发和测试。

This proposal is directed toward improving our understanding of factors associated with neonatal lung injury and its long term clinical consequences. The component projects will examine the basis of acute lung injury as well as the sequence of injury that result in long term structural and functional alterations of the airway. The Center will include 6 major projects in addition to defined cores for administrative and programmatic needs of the Center. Specific projects are: 1) Neonatal Lung Matrix Drives Lung Repair. This study will define the influence of oxidant injury on lung epithelial basement membrane matrix interactions; 2) Alveolar Epithelial Differentiation in Oxidant Injury. This study will examine the influence of oxidant injury on Na+/K+ ATPase and gammaglutamyltransferase in lung; 3) Relationship Between Stress Proteins and Antioxidants in Hyperoxia. The heat shock response has been shown to be important in a variety of systems involved in injury and repair. We will examine heat shock proteins in relationship to endogenous antioxidant mechanisms following hyperoxic insult; 4) Regulation of Surfactant Phospholipid Metabolism in Injured Adult and Developing Lungs. This project will examine surfactant phospholipid synthesis in different populations of type II cells following silica induced lung injury; 5) The Influence of Butyrate Acid on SP-A Gene Transcription. This project will study the response of lung to a specific biochemical insult associated with alterations in gene expression; 6) Energetics of Breathing in Infants with Chronic Lung Disease. In this project, we will study alterations in lung work, respiratory efficiency and energy expenditure in infants with BPD who represent the final common pathway of acute lung injury. The SCOR will include 2 Cores which will provide support for the programmatic, educational, and oversight components as well as biostatistical support and a shared instrument facility. A shared morphology and electron microscopy core will provide support for the component laboratory projects. The interactions and shared knowledge provided through the Center will lead to a better understanding of the events underlying lung injury that will be essential before rational strategies for prevention can be rigorously developed and tested.